Bump Ahead? Ozempic and Fertility Explained
Evelyn is a 28-year-old female with a history of polycystic ovary syndrome (PCOS) who flashed her new 2 karat engagement ring at our visit last week. She lost 40 pounds on Wegovy over a one-year span. Her once irregular periods were now 28 days apart, and her male hormones had normalized. She preferred to stop her oral birth control shortly after her upcoming wedding and wanted to know the following:
When she was younger, she was told by her ob/gyn that her fertility would be compromised because of her PCOS diagnosis. How did her substantial weight loss due to GLP-1 receptor agonists affect her fertility?
How many weeks before trying to conceive did she have to stop her Wegovy and why?
Were there any studies to show that it is safe to take Wegovy during pregnancy because she was terrified to stop it and gain back those 40 pounds?
While data are lacking, I tried to give her as much evidence-based information as possible.
Fertility
A multicenter study conducted in 2007 by the NIH showed that being overweight corresponds to an 8% reduction in the likelihood of achieving pregnancy within one menstrual cycle. Similarly, an obesity diagnosis leads to a 16% reduction in that same likelihood.[1]
The 2022 Fit-Plese trial at Penn State College of Medicine investigated the effects of weight loss interventions on fertility outcomes in patients without underlying insulin resistance and PCOS. Although participants achieved significant weight reduction, improvements in fertility were not consistently observed.[2]
By contrast, weight loss clearly improves fertility in patients with PCOS by reducing insulin resistance.[3] Insulin resistance is associated with elevated insulin levels, which in turn increase the production of male hormones. These elevated male hormones often inhibit ovulation. When insulin sensitivity is restored through weight loss, the reproductive hormones normalize, allowing ovulation to occur. Insulin resistance occurs more frequently in women with PCOS regardless of their obesity status.[4] PCOS patients with insulin resistance may benefit from GLP-1 receptor agonists, which improve insulin sensitivity and promote weight loss, thereby resetting the hormonal balance.[5]
Stopping GLP-1 receptor agonists before conception
Patients eliminate medication from the body at different rates. On average, it takes 6 weeks to fully clear GLP 1 from the system. Both Novo Nordisk and Eli Lilly recommend discontinuing these medicines (Ozempic/Wegovy; Mounjaro) at least two months before attempting to conceive. These recommendations were formalized in 2022 for Ozempic/Wegovy and in 2023 for Mounjaro. In 2023, the UFDA advised women to stop taking GLP-1 drugs at least two months before conception.
Taking GLP 1 receptor agonists during pregnancy
There are no human studies looking at the rate of miscarriage on these drugs, but animal studies have reported a higher risk. This may be an indirect effect of weight loss in the animals rather than a direct effect of the medication.
Every pregnancy has a 3-5% chance of having a birth defect. Human studies have not been performed to see if these medications increase the risk of birth defects. Animal studies did report a higher risk of birth defects, but again, this may be an indirect effect of weight loss in the animals rather than a direct effect of the medication.
Patients often share their experiences getting pregnant while take Ozempic on Facebook groups and Reddit. Many women write about unwittingly taking GLP-1 receptor agonists during pregnancy without any ill effects. One woman on Reddit took Ozempic until 23 weeks’ gestation, and she delivered a healthy baby.
Novo Nordisk and Eli Lilly are developing comprehensive pregnancy registries to track the safety of these medications during pregnancy. These registries will gather real world data to better understand the effects of these medicines on maternal and fetal health and will hopefully give us much needed answers as early as 2027.
Evelyn felt very reassured that her fertility likely normalized in the setting of GLP-1- induced weight loss. Based on the prevailing data, she agreed to stop her Wegovy at least 8 weeks prior to conception. I prescribed metformin for her to take after stopping Wegovy to help preserve insulin sensitivity and decrease the risk of rebound weight gain. I also referred her to my team of dietitians, trainers, and health coaches to help her maintain a healthy body weight while trying to conceive.
It's still in the early days in Evelyn’s journey towards motherhood, but I’m glad she’s approached it with a plan tailored to her specific needs and based on the latest scientific evidence.
[1] Gesink Law DC et al. Obesity and time to pregnancy. Hum Reprod2007;22:414-20. doi:10.1093/humrep/del400. https://pubmed.ncbi.nlm.nih.gov/17095518/ pmid:17095518
[2] Legro RS et al. Reproductive Medicine Network. Effects of preconception lifestyle intervention in infertile women with obesity: The FIT-PLESE randomized controlled trial. PLoS Med2022;19:e1003883. doi:10.1371/journal.pmed.1003883.
[3] Legro RS et al. Benefit of delayed fertility therapy with preconception weight loss over immediate therapy in obese women with PCOS. J Clin Endocrinol Metab2016;101:2658-66. doi:10.1210/jc.2016-1659.
[4] Marshall JC et al. Should all women with PCOS be treated for insulin resistance? Fertil Steril2012;97:18-22. doi:10.1016/j.fertnstert.2011.11.036.
[5] Sachdeva G et al. Comparison of the different PCOS phenotypes based on clinical metabolic, and hormonal profile, and their response to clomiphene. Indian J Endocrinol Metab. 2019;23:326-31. doi:10.4103/ijem.IJEM_30_19.